Genome-wide scans for selection signatures in indigenous chickens reveal candidate genes associated with local adaptation.

Population growth and climate change pose challenges to the sustainability of poultry farming. The emphasis on high-yield traits in commercialized breeds has led to a decline in their adaptability. Chicken varieties adapted to the local environment, possessing traits that facilitate adaptation to climate change, such as disease resistance and tolerance to extreme weather conditions, can improve hybridization outcomes. In this study, we conducted an analysis of the population structure and genetic diversity of 110 chickens representing indigenous breeds from southern China and two different commercial breeds. Further, we performed comparative population genomics, utilizing nucleotide diversity and fixation statistics, to characterize genomic features of natural selection and to identify unique genetic traits and potential selection markers developed by indigenous breeds after adapting to the local environment. Results based on genetic diversity and population structure analyses showed that indigenous varieties exhibited high levels of genetic diversity. Commercial breeds that have been indigenously bred demonstrated higher levels of genetic diversity than those that have not, and breeds with different selection practices displayed significant differences in genetic structure. Additionally, we further searched for potential genomic regions in native chicken ecotypes, uncovering several candidate genes related to ecological adaptations affecting local breeds, such as IKBKB, S1PR1, TSHR, IL1RAPL1 and AMY2A, which are involved in disease resistance, heat tolerance, immune regulation and behavioral traits. This work provides important insights into the genomic characterization of ecotypes of native chicken in southern China. The identification of candidate genes associated with traits such as disease resistance, heat tolerance, immunomodulation, and behavioral traits is a significant outcome. These candidate genes may contribute to the understanding of the molecular basis of the adaptation of the southern native chicken to the local environment. It is recommended that these genes be integrated into chicken breeding programs to enhance sustainable agriculture and promote effective conservation and utilization strategies.

Preparation and characterisation of novel casein-gum Arabic composite microcapsules for targeted in vivo delivery of Lactiplantibacillus plantarum A3.

The health benefits of probiotics in the body are predicated on their ability to remain viable in harsh gastrointestinal conditions and complex pathological microenvironments. Casein and gum Arabic (GA), with dual emulsifying and stabilising effects in colloidal systems. Therefore, the objective of this research was to develop a novel microcapsule to encapsulate Lactiplantibacillus plantarum A3 using casein and GA as wall materials to improve the survival of the bacteria during gastrointestinal digestion, storage and lyophilization. The casein and GA composite microcapsules were prepared and characterised by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM). It was found that the microcapsules had stable morphology, uniform size and spherical shape. The results revealed that the encapsulation of microcapsules significantly improved the survival of L. plantarum A3 in gastrointestinal fluid environment (5.52 × 109 cfu/ml) and lyophilization treatment (6.25 × 109 cfu/ml). Furthermore, the microencapsulated L. plantarum A3 exhibited an improved ability to regulate intestinal microbiota by effectively increasing the relative abundance of Bacteroidetes, Proteobacteria and Actinobacteria and decreasing the relative abundance of Firmicutes in vivo. The findings of the study will help to design a lactic acid bacteria encapsulation system based on the gastrointestinal environment and provide a basis for the development of probiotic functional products.

Quantifying hospital environmental ventilation using carbon dioxide monitoring - a multicentre study.

The COVID-19 pandemic has highlighted the importance of environmental ventilation in reducing airborne pathogen transmission. Carbon dioxide monitoring is recommended in the community to ensure adequate ventilation. Dynamic measurements of ventilation quantifying human exhaled waste gas accumulation are not conducted routinely in hospitals. Instead, environmental ventilation is allocated using static hourly air change rates. These vary according to the degree of perceived hazard, with the highest change rates reserved for locations where aerosol-generating procedures are performed, where medical/anaesthetic gases are used and where a small number of high-risk infective or immunocompromised patients may be isolated to reduce cross-infection. We aimed to quantify the quality and distribution of ventilation in hospital by measuring carbon dioxide levels in a two-phased prospective observational study. First, under controlled conditions, we validated our method and the relationship between human occupancy, ventilation and carbon dioxide levels using non-dispersive infrared carbon dioxide monitors. We then assessed ventilation quality in patient-occupied (clinical) and staff break and office (non-clinical) areas across two hospitals in Scotland. We selected acute medical and respiratory wards in which patients with COVID-19 are cared for routinely, as well as ICUs and operating theatres where aerosol-generating procedures  are performed routinely. Between November and December 2022, 127,680 carbon dioxide measurements were obtained across 32 areas over 8 weeks. Carbon dioxide levels breached the 800 ppm threshold for 14% of the time in non-clinical areas vs. 7% in clinical areas (p < 0.001). In non-clinical areas, carbon dioxide levels were > 800 ppm for 20% of the time in both ICUs and wards, vs. 1% in operating theatres (p < 0.001). In clinical areas, carbon dioxide was > 800 ppm for 16% of the time in wards, vs. 0% in ICUs and operating theatres (p < 0.001). We conclude that staff break, office and clinical areas on acute medical and respiratory wards frequently had inadequate ventilation, potentially increasing the risks of airborne pathogen transmission to staff and patients. Conversely, ventilation was consistently high in the ICU and operating theatre clinical environments. Carbon dioxide monitoring could be used to measure and guide improvements in hospital ventilation.

Comparison of cytological adequacy in ultrasound-guided fine-needle aspiration of thyroid nodules with different numbers of needle passes.

OBJECTIVE: The aim of this study was to compare the cytological adequacy rates of different needle passes in ultrasound-guided fine-needle aspiration biopsy of thyroid nodules and, thus, to help establish the criterion for selecting the number of needle passes according to the characteristics of thyroid nodules. PATIENTS AND METHODS: This single-center and randomized prospective study involved 207 consecutive patients with 240 solid or predominantly solid thyroid nodules. These nodules were randomly divided into a 1-pass group, a 2-pass group, and a 3-pass group. Then the nodules were sent for cytopathological diagnosis, and cytological results were classified according to the Bethesda classification. Bethesda I was defined as inadequate, and Bethesda Ⅱ-Ⅵ were defined as adequate. Then the cytological adequacy rates of different groups were compared. RESULTS: In total, 221 nodule specimens were considered as adequate and 19 nodule specimens inadequate. The overall adequacy rate was 92.1%. However, there were no significant differences among the 1, 2, and 3-pass groups in terms of adequacy rates (91.3%, 92.5%, and 92.5%, respectively). CONCLUSIONS: The number of needle passes does not significantly affect the cytological adequacy in ultrasound-guided fine-needle aspiration of solid or predominantly solid thyroid nodules. The cytological adequacy of one-needle pass is comparable to those of two and three-needle passes.

Major Fusarium species and mycotoxins associated with freshly harvested maize grain in Uruguay.

Fusarium species are common fungal pathogens of maize. Fusarium graminearum and Fusarium verticillioides, among others, can cause maize ear rot, and they are also mycotoxin producers. The aims of this work were to determine the frequency and diversity of Fusarium species in Uruguayan maize kernels, evaluate the toxigenic potential of the isolates, determine toxin contamination levels on freshly harvested grain, and assess the sensitivity of main Fusarium species against fungicides. Fusarium verticillioides was the most frequent species isolated, followed by Fusarium graminearum sensu stricto. Of F. verticillioides isolates studied for fumonisin production, 72% produced fumonisin B1 and 32% fumonisin B2. Considering in vitro toxin production by F. graminearum sensu stricto isolates, deoxynivalenol was the main toxin produced, followed by zearalenone and nivalenol. Fumonisins were the most frequently found toxins on freshly harvested maize samples (98% in 2018 and 86% in 2019), and also, fumonisin B1 was the toxin with highest concentration in both years studied (4860 µg/kg in 2018 and 1453 µg/kg in 2019). Deoxynivalenol and zearalenone were also found as contaminants. Metconazole and epoxiconazole were the most effective fungicides tested on F. verticillioides isolates. Fusarium graminearum sensu stricto isolates also were more sensitive to metconazole compared to other fungicides; nevertheless, epoxiconazole was less efficient in controlling this species. This is the first study that reports Fusarium species and mycotoxin contamination levels associated with maize grain in Uruguay. Its detection is the main step to develop management strategies in order to minimize fungal infection in maize crops.

[Multimodal imaging features of acute macular retinopathy in patients with COVID-19].

Objective: To investigate the multimodal imaging characteristics of acute macular retinopathy (AMR) and/or parafoveal acute middle maculopathy (PAMM) in patients with coronavirus disease 2019 (COVID-19). Methods: It was a cross-sectional study. Eight patients (15 eyes) diagnosed with AMN and/or PAMM, who presented for their initial visit at Kaifeng Eye Hospital between December 17 and December 31, 2022 and were also confirmed positive for COVID-19, were enrolled as the observation group. The patients were classified into four types based on swept-source optical coherence tomography (SS-OCT) findings. Fifteen healthy volunteers (15 eyes) without ocular or systemic diseases were recruited as the healthy control group, and one eye was randomly selected for analysis. All participants underwent detailed ophthalmic examinations, including best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus photography (FP), intraocular pressure measurement, fundus infrared imaging, OCT and OCT angiography (OCTA). The foveal avascular zone (FAZ) area of the macular center was measured. General information and multimodal imaging findings were collected and analyzed. The superficial capillary plexus vessel density (SCP-VD) and deep capillary plexus vessel density (DCP-VD) were measured in circular areas with diameters of 1.0 mm, >1.0 mm and ≤3.0 mm, and>3.0 mm and ≤6.0 mm centered on the foveal center, recorded as SCP-VD1.0, 3.0, 6.0 and DCP-VD1.0, 3.0, 6.0. Statistical analyses were performed using t-tests, Mann-Whitney U tests, and chi-square tests. Results: The observation group consisted of 6 males (11 eyes) and 2 females (4 eyes) with a mean age of (26.87±11.56) years. The healthy control group included 11 males (11 eyes) and 4 females (4 eyes) with a mean age of (28.75±12.30) years. There were no statistically significant differences in age and gender distribution between the two groups (all P>0.05). All patients in the observation group experienced high fever (≥39.0 ℃) and developed ocular symptoms during the febrile period or within 24 hours after fever resolution. Among all patients, there were 5 cases (7 eyes) of Type Ⅰ, 1 case (1 eye) of Type Ⅱ, 3 cases (4 eyes) of Type Ⅲ, and 2 cases (3 eyes) of Type Ⅳ. In Type Ⅲ and Ⅳ, 3 cases (4 eyes) exhibited weakly reflective cystic spaces in the outer plexiform or outer nuclear layers, and fundus photography revealed multiple gray or reddish-brown lesions in the macular region. One case (1 eye) showed retinal superficial hemorrhage. Cotton wool spots were observed in 2 cases (4 eyes). Fundus infrared imaging showed that Type Ⅰ manifested as weak reflectivity lesions in the parafoveal central zone, with the tip pointing towards the fovea. Type Ⅱ showed no apparent abnormalities in the macular region, while Type Ⅲ and Ⅳ displayed map-like weak reflective lesions spanning the foveal center. OCTA findings demonstrated that SCP-VD1.0 in the observation group was 6.93% (4.77%, 6.93%), significantly lower than the healthy control group's 10.66% (8.05%, 10.55%) (U=174.00, P=0.016). SCP-VD3.0 in the observation group was 37.14% (32.15%, 43.48%), also lower than the healthy control group's 43.06% (38.95%, 46.55%) (U=174.00, P=0.016). DCP-VD3.0 in the observation group was 48.20% (46.11%, 50.33%), lower than the healthy control group's 51.10% (50.04%, 53.02%) (U=188.00, P=0.009). DCP-VD6.0 in the observation group was 49.27% (47.26%, 51.67%), lower than the healthy control group's 52.43% (50.07%, 53.82%) (U=70.00, P=0.004). There were no significant differences in SCP-VD6.0 and DCP-VD1.0 between the two groups (both P>0.05). Conclusions: Acute macular retinopathy in patients with COVID-19 can involve all retinal layers and present as segmental hyper-reflectivity on SS-OCT. Fundus infrared imaging reveals weak reflectivity in the affected area, fundus photography shows multiple gray or reddish-brown lesions in the macular region, and OCTA demonstrates a decrease in SCP-VD and DCP-VD.

[Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China].

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

On a new species of freshwater crab from southern China (Crustacea, Brachyura, Potamidae).

A new species of potamid freshwater crab of the genus Indochinamon Yeo & Ng, 2007, is described from a recent collection in Yunnan Province, China. Indochinamon frontatum sp. nov. is distinguished from congeners by the form of the carapace, notably in the features of the convex frontal region, and distinctively structured male first gonopod. Molecular data derived from the mitochondrial 16S rDNA supports the recognition of the taxon.

A Southeast Asian collaborative Delphi consensus on surveying risk factors for head and neck cancer screening and prevention.

The objective of this study was to determine high value questions for early detection and prevention of head and neck cancer by querying content experts on patient risk factors relevant to local communities in Southeast Asia (i.e., Vietnam, Laos, China, and Singapore). The Delphi method was employed using three rounds of asynchronous surveying which included participants among five different collaborating medical centers. 60 total survey items were assessed for consensus defined by a priori measures on the relative level of value of these questions for use in head and neck cancer screening. 77% of items reached a consensus and no items were concluded to be of low value despite differences in conclusions regarding relative importance. Survey items focused on patient demographic information and physical examination were examined across variables such as expert department affiliation, academic designation, and years of experience and found to be without statistically significant differences. However, with consensus items related to social risk factors, it was determined that participants who had 15 or more years of experience or identified as otolaryngologists rated these items at a relatively lower value than their peers with less experience (p < 0.0001, p = 0.0017) or outside the field of otolaryngology (p = 0.0101). This study explicitly identifies patient variables to consider in head and neck cancer screening that have not previously been comprehensively or methodically assessed in current literature. Increasing awareness of these risk factors may benefit the design and implementation of future head and neck cancer early detection and prevention programs in Southeast Asia and beyond as well as positively impact head and neck cancer outcomes.

Small-molecule inhibitors of P-Rex guanine-nucleotide exchange factors.

P-Rex1 and P-Rex2 are guanine-nucleotide exchange factors (GEFs) that activate Rac small GTPases in response to the stimulation of G protein-coupled receptors and phosphoinositide 3-kinase. P-Rex Rac-GEFs regulate the morphology, adhesion and migration of various cell types, as well as reactive oxygen species production and cell cycle progression. P-Rex Rac-GEFs also have pathogenic roles in the initiation, progression or metastasis of several types of cancer. With one exception, all P-Rex functions are known or assumed to be mediated through their catalytic Rac-GEF activity. Thus, inhibitors of P-Rex Rac-GEF activity would be valuable research tools. We have generated a panel of small-molecule P-Rex inhibitors that target the interface between the catalytic DH domain of P-Rex Rac-GEFs and Rac. Our best-characterized compound, P-Rex inhibitor 1 (PREX-in1), blocks the Rac-GEF activity of full-length P-Rex1 and P-Rex2, and of their isolated catalytic domains, in vitro at low-micromolar concentration, without affecting the activities of several other Rho-GEFs. PREX-in1 blocks the P-Rex1 dependent spreading of PDGF-stimulated endothelial cells and the production of reactive oxygen species in fMLP-stimulated mouse neutrophils. Structure-function analysis revealed critical structural elements of PREX-in1, allowing us to develop derivatives with increased efficacy, the best with an IC50 of 2 µM. In summary, we have developed PREX-in1 and derivative small-molecule compounds that will be useful laboratory research tools for the study of P-Rex function. These compounds may also be a good starting point for the future development of more sophisticated drug-like inhibitors aimed at targeting P-Rex Rac-GEFs in cancer.

[Atorvastatin inhibits malignant behaviors and induces apoptosis in human glioma cells by up-regulating miR-146a and inhibiting the PI3K/Akt signaling pathway].

OBJECTIVE: To explore the effect of atorvastatin (AVT) on biological behaviors and the miR-146a/PI3K/Akt signaling pathway in human glioma cells. METHODS: Human glioma U251 cells were treated with 8.0 µmol/L AVT or transfected with a miR-146a inhibitor or a negative control fragment (miR-146a NC) prior to AVT treatment. RT-PCR was used to detect miR-146a expression in the cells, and the changes in cell proliferation rate, apoptosis, cell invasion and migration were detected using MTT assay, flow cytometry, and Transwell assay. Western blotting was performed to detect the changes in cellular expressions of proteins in the PI3K/Akt signaling pathway. RESULTS: AVT treatment for 48 h resulted in significantly increased miR-146a expression and cell apoptosis (P < 0.01) and obviously lowered the cell proliferation rate, invasion index, migration index, and expressions of p-PI3K and p-Akt protein in U251 cells (P < 0.01). Compared with AVT treatment alone, transfection with miR-146a inhibitor prior to AVT treatment significantly reduced miR-146a expression and cell apoptosis (P < 0.01), increased the cell proliferation rate, promoted cell invasion and migration, and enhanced the expressions of p-PI3K and p-Akt proteins in the cells (P < 0.01); these effects were not observed following transfection with miR-146a NC group (P>0.05). CONCLUSION: AVT can inhibit the proliferation, invasion and migration and promote apoptosis of human glioma cells possibly by up-regulating miR-146a expression and inhibiting the PI3K/Akt signaling pathway.

Hypochloraemia following admission to hospital with heart failure is common and associated with an increased risk of readmission or death: a report from OPERA-HF.

AIMS: Hypochloraemia is common in patients hospitalized with heart failure (HF) and associated with a high risk of adverse outcomes during admission and following discharge. We assessed the significance of changes in serum chloride concentrations in relation to serum sodium and bicarbonate concentrations during admission in a cohort of 1002 consecutive patients admitted with HF and enrolled into an observational study based at a single tertiary centre in the UK. METHODS AND RESULTS: Hypochloraemia (<96 mmol/L), hyponatraemia (<135 mmol/L), and metabolic alkalosis (bicarbonate >32 mmol/L) were defined by local laboratory reference ranges. Outcomes assessed were all-cause mortality, all-cause mortality or all-cause readmission, and all-cause mortality or HF readmission. Cox regression and Kaplan-Meier curves were used to investigate associations with outcome. During a median follow-up of 856 days (interquartile range 272-1416), discharge hypochloraemia, regardless of serum sodium, or bicarbonate levels was associated with greater all-cause mortality [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.15-1.79; P = 0.001], all-cause mortality or all-cause readmission (HR 1.26, 95% CI 1.04-1.53; P = 0.02), and all-cause mortality or HF readmission (HR 1.41, 95% CI 1.14-1.74; P = 0.002) after multivariable adjustment. Patients with concurrent hypochloraemia and natraemia had lower haemoglobin and haematocrit, suggesting congestion; those with hypochloraemia and normal sodium levels had more metabolic alkalosis, suggesting decongestion. CONCLUSION: Hypochloraemia is common at discharge after a hospitalization for HF and is associated with worse outcome subsequently. It is an easily measured clinical variables that is associated with morbidity or mortality of any cause.

[Inhibition of TGF-ß promotes functional recovery of spinal cord injury in mice by reducing fibronectin deposition].

OBJECTIVE: To investigate the effect of transforming growth factor (TGF-ß) inhibition on functional recovery of spinal cord injury in mice. METHODS: Twelve mice were divided into treatment group, control group and sham-operated group (n=4). The mice in the treatment group were subjected to hemisection of the spinal cord and received intraperitoneal injection of TGF-ß neutralizing antibody (1D11) 3 times a week (25 µL each time), and those in control group were injected with the vehicle antibody (13C4) following spinal cord hemisection. The sham-operated mice underwent sham operation to expose the spinal cord without hemisection. Four weeks later, the heart of the mice was perfused and 1-2 cm of the spinal cord spanning the injury site was harvested. Immunofluorescence staining of FSP1, fibronectin, and PGP9.5 was performed to assess fibroblast recruitment in the injury area, fibronectin deposition, and neurological recovery. For further verification of the results, we used a mouse model of spinal cord clamp injury to observe the survival of axons and distribution of astrocytes by detecting expressions of 5-HT and GFAP with immunofluorescence assay. RESULTS: In the hemisection injury model, fibroblasts recruitment and fibronectin deposition in the injured area was significantly reduced and the neurological function was improved in 1D11 treatment group as compared with those in 13C4-treated group (P < 0.05). In the spinal cord clamp injury model, treatment with 1D11, as compared with the 13C4, resulted in significantly increased number of 5-HT-positive axons with extended axonal length and obviously increased the number of GFAP-positive astrocytes in the injured area (P < 0.05). CONCLUSION: Inhibiting TGF-ß after spinal cord injury can reduce the recruitment of fibroblasts and fibronectin deposition to promote recovery of neurological function and repair of the injured spinal cord in mice.

Alcohol, coffee and tea intake and the risk of cognitive deficits: a dose-response meta-analysis.

AIMS: Lifestyle interventions are an important and viable approach for preventing cognitive deficits. However, the results of studies on alcohol, coffee and tea consumption in relation to cognitive decline have been divergent, likely due to confounds from dose-response effects. This meta-analysis aimed to find the dose-response relationship between alcohol, coffee or tea consumption and cognitive deficits. METHODS: Prospective cohort studies or nested case-control studies in a cohort investigating the risk factors of cognitive deficits were searched in PubMed, Embase, the Cochrane and Web of Science up to 4th June 2020. Two authors searched the databases and extracted the data independently. We also assessed the quality of the studies with the Newcastle-Ottawa scale. Stata 15.0 software was used to perform model estimation and plot the linear or nonlinear dose-response relationship graphs. RESULTS: The search identified 29 prospective studies from America, Japan, China and some European countries. The dose-response relationships showed that compared to non-drinkers, low consumption (<11 g/day) of alcohol could reduce the risk of cognitive deficits or only dementias, but there was no significant effect of heavier drinking (>11 g/day). Low consumption of coffee reduced the risk of any cognitive deficit (<2.8 cups/day) or dementia (<2.3 cups/day). Green tea consumption was a significant protective factor for cognitive health (relative risk, 0.94; 95% confidence intervals, 0.92-0.97), with one cup of tea per day brings a 6% reduction in risk of cognitive deficits. CONCLUSIONS: Light consumption of alcohol (<11 g/day) and coffee (<2.8 cups/day) was associated with reduced risk of cognitive deficits. Cognitive benefits of green tea consumption increased with the daily consumption.

Uncovering the differentially expressed genes and pathways involved in the progression of stable coronary artery disease to acute myocardial infarction using bioinformatics analysis.

OBJECTIVE: Coronary artery disease (CAD) is the main cause of mortality worldwide. How stable coronary artery disease (SCAD) progresses to acute myocardial infarction (AMI) is not known. This study was aimed to explore the differentially expressed genes (DEGs) and pathways involved in the progression of SCAD to AMI. MATERIALS AND METHODS: Publicly available gene-expression profiles (GSE71226, GSE97320, GSE66360) were downloaded from the Gene Expression Omnibus (GEO) database and integrated to identify DEGs. The GSE59867 dataset was further used to verify the result of screened DEGs. Functional-enrichment analyses, protein-protein interaction network, microRNA-transcription factor (TF)-mRNA regulatory network, and drug-gene network were visualized. RESULTS: Sixty common DEGs (CDEGs) were screened between the SCAD-Control group and AMI-Control group in the integrated dataset. Four upregulated DEGs were selected from GSE59867. Twenty hub genes were discovered, and three significant modules were constructed in the PPI network. The intersection of functional and pathway-enrichment analyses of 60 CDEGs and the module DEGs indicated that they were mainly involved in "inflammatory response", "immune response", and "cytokine-cytokine receptor interaction". A miRNA-TF-mRNA regulatory network comprised 87 miRNAs, 16 upregulated target DEGs and 7 TFs. CONCLUSIONS: We identified several important genes and miRNAs involved in the progression of SCAD to AMI: platelet activating factor receptor (PTAFR), aquaoporin-9 (AQP9), toll-like receptor-4 (TLR4), human constitutive androstane receptor-3 (HCAR3), leucine-rich-α2 glycoprotein-1 (LRG1), mothers Against Decapentaplegic Homolog 4 (SMAD4) and miRNA-149-5p, miRNA-6778-3p, and miRNA-520a-3p. Inflammation and the immune response had important roles in the progression from SCAD to AMI.

Identification of the pivotal differentially expressed genes and pathways involved in Staphylococcus aureus-induced infective endocarditis by using bioinformatics analysis.

OBJECTIVE: Infective endocarditis (IE), particularly by Staphylococcus aureus, is an uncommon bacteremia-associated infection of the endocardium and cardiac valves. Herein, we evaluated predictive noninvasive biomarkers for IE caused by S. aureus through bioinformatics analysis. MATERIALS AND METHODS: Staphylococcus aureus-associated and IE-associated differentially expressed genes (DEGs) were identified by bioinformatics analysis of the GSE6269 and GSE29161 Gene Expression Omnibus (GEO) datasets. The DEGs were analyzed with the LIMMA package, and the coregulated genes were chosen as the intersection of DEGs between the two datasets, called common differentially expressed genes (CDEGs). The enrichment study of CDEGs was subsequently performed with the DAVID and KOBAS web resources. Finally, protein-protein interaction (PPI) network, microRNA (miRNA)-transcription factor (TF)-mRNA (messenger RNA) regulatory network, and the network of drug-genes were identified. RESULTS: From GSE6269 and GSE29161, respectively, a total of 201 and 741 DEGs were obtained. Gene Ontology (GO) analysis showed that CDEGs were primarily involved in innate immune response, extracellular exosome, as well as calcium ion binding, while the pathway analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that CDEGs were significantly enriched in the B-cell receptor, IL-17, and NF-kappa B signaling pathways. The hub genes in the PPI network included HP, S100A12, SPI1, CD14, CCR1, S100A9 and so on. In the miRNA-TF-mRNA regulatory network, SPI1 could target miR-361-5p, miR-155-5p, and miR-339-5p in the progression of IE. CONCLUSIONS: Several pivotal genes and pathways were identified in the progression of S. aureus-induced IE, which may have the potential for early detection.

Long noncoding RNA SNHG14 regulates ox-LDL-induced atherosclerosis cell proliferation and apoptosis by targeting miR-186-5p/WIPF2 axis.

To investigate the role of small nucleolus RNA host gene 14 (SNHG14) in the progression of atherosclerosis (AS), bioinformatics analysis, and other relevant experiments (cell counting kit-8, flow cytometry, quantitative real-time polymerase chain reaction, luciferase reporter, RNA immunoprecipitation, RNA pull-down, and western blot assays) were done. The current study revealed that SNHG14 level was high in the serum of AS patients and oxidized low-density lipoprotein (ox-LDL)-induced AS cell lines. Besides, we found that SNHG14 accelerated cell proliferation while inhibited cell apoptosis in ox-LDL-induced AS cell lines. Next, SNHG14 was confirmed to be a sponge for miR-186-5p in AS cells, and it was validated that SNHG14 regulated AS cell proliferation and apoptosis by sponging miR-186-5p. Moreover, we uncovered that WAS-interacting protein family member 2 (WIPF2) was a downstream target of miR-186-5p in AS cells. Finally, it was demonstrated that miR-186-5p modulated AS cell proliferation and apoptosis via targeting WIPF2. To conclude, our research disclosed that SNHG14 affected ox-LDL-induced AS cell proliferation and apoptosis through miR-186-5p/WIPF2 axis, which may provide a theoretical basis for the treatment and diagnosis of AS.

MicroRNA-130b inhibits cerebral ischemia/reperfusion induced cell apoptosis via regulation of IRF1.

OBJECTIVE: Cerebral ischemia/reperfusion (CIR) frequently causes serious disabilities and correlates with certain neurological processes. Some studies have shown that microRNAs (miRNAs) exert a neuroprotective effect by modulating the inflammatory process in CIR. However, the biofunction and the mechanism of miR-130b in CIR need to be fully elucidated. MATERIALS AND METHODS: An oxygen-glucose deprivation/reperfusion (OGD/R) model was constructed using SH-SY5Y cell line to analyze the function of miR-130b in CIR. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine the expression levels of miR-130b and IRF1. Western blot was performed to detect the protein levels of IRF1, Bax, and Bcl-2. Cell viability was determined using MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays. Dual-Luciferase reporter assay was conducted to confirm the target gene of miR-130b. RESULTS: In this study, we found that miR-130b level was prominently decreased after treatment with OGD/R. Through gain and loss assays, we concluded that miR-130b restoration promoted cell proliferation and inhibited cell apoptosis in OGD/R-treated cells. Moreover, we also identified IRF1 as an important target of miR-130b. Additionally, IRF1 knockdown remarkably abrogated the protection mediated by miR-130b against the injuries in OGD/R-treated cells. CONCLUSIONS: Taken together, our results suggested that miR-130b facilitated cell viability and suppressed cell apoptosis of CIR via negatively regulating of IRF1.

LncRNA XIST regulates cell proliferation, migration and invasion of glioblastoma via regulating miR-448 and ROCK1.

Long non-coding ribonucleic acids (lncRNAs) have been recognized as markers in several cancers and play important roles in glioblastoma (GBM). But the role of lncRNA X inactive-specific transcript (XIST) in GBM and its possible mechanisms are rarely studied in depth. This study was conducted to explore the detailed roles of XIST in cell proliferation, migration, and invasion of GBM. Expressions of XIST, miR-448, and ρ associated coiled coil containing protein kinase 1 (ROCK1) were detected by qRT-PCR or Western blot in A172 and U251 cells. The interactions among XIST, miR-448 and ROCK1 were verified through luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Cell Counting Kit-8 (CCK-8) assay and Transwell assay were introduced to detect how XIST knockdown, miR-448 overexpression, or along with ROCK1 overexpression affect cellular malignancy of GBM cells. XIST and ROCK1 were up-regulated while miR-448 expression was decreased in GBM cells. XIST knockdown or miR-448 overexpression could dramatically inhibit GBM cell proliferation, migration, and invasion. Moreover, XIST negatively regulated miR-448 expression through the function as competing endogenous RNA (ceRNA), thus leading to the up-regulation of ROCK1, one miR-448 target gene. Moreover, ROCK1 overexpression could reverse the suppression of XIST knockdown or miR-448 upregulation on cellular malignancy. In brief, the effects of XIST may promote cellular malignancy of GBM through miR-448/ROCK1 axis, which will provide new understanding of GBM pathogenesis and progression.

Prunella vulgaris L protects glucocorticoids-induced osteogenesis inhibition in bone marrow mesenchymal stem cells through activating the Smad pathway.

OBJECTIVE: To elucidate the role of Prunella vulgaris L (PVL) in protecting glucocorticoids (GC)-induced osteogenesis inhibition, thereafter, protecting the deterioration of osteoporosis (OP). MATERIALS AND METHODS: Cell Counting Kit-8 (CCK-8) assay was conducted to assess the influence of PVL treatment on MSCs viability. Osteogenesis in MSCs was induced by Dexamethasone (DEX) stimulation. Regulatory effects of PVL on osteogenesis-related gene expressions, ALP activity, and mineralization ability in DEX-induced MSCs were determined. At last, protein levels of p-Smad1/5/9 and total-Smad1/5/9 influenced by DEX and PVL were measured by Western blot. RESULTS: PVL treatment did not pose a time- or dose-dependent influence on MSCs viability. DEX induction in MSCs downregulated ALP, RUNX2, Bglap, and Osterix. ALP activity and mineralization in DEX-induced MSCs were suppressed. Downregulated osteogenesis-related genes decreased ALP activity and mineralization in MSCs undergoing DEX stimulation were partially reversed by PVL treatment. Moreover, the downregulated p-Smad1/5/9 level in DEX-induced MSCs was elevated by PVL treatment, while total-Smad1/5/9 was not affected. CONCLUSIONS: PVL alleviated GC-induced suppression in MSCs osteogenesis by activating the Smad pathway, thereafter, protecting the deterioration of OP.